In 2010, over 11.5 million people were living with cancer in the United States and over 500,000 new cases are expected to be diagnosed each year. The life threatening and unpredictable course of cancer makes it a particularly stressful lif experience. Stress may be defined as when the demands being placed on an individual are perceived as threatening or harmful and exceed the resources available to manage the stressor. Decades of research have shown that stress is associated with maladaptive health behaviors (e.g., high fat diet) as well as increased risk of morbidity and mortality. The goal of this prospective study is to examine the mechanistic pathways linking chronic stress and engagement in maladaptive health behaviors with disease progression in people diagnosed with hepatobiliary carcinoma. The proposed study will begin to elucidate the biobehavioral pathways linking stress and health behaviors with disease progression in the context of cancer. The aims and hypotheses of this study are: (1) to investigate predictors of the psychological and physiological stress response to a diagnosis or recurrence of hepatobilary carcinoma. We expect that people who report a past history of early adverse events (e.g., death of a loved one, abuse) will report higher levels of perceived stress and elevations in biomarkers of inflammation. Early adverse events are expected to be associated with an earlier age of onset of these maladaptive health behaviors (e.g., alcohol use) and contributed to the risk factors associated with the development of cancer (e.g., cirrhosis); (2) to examine the dynamic link between stress and health behaviors over time in people diagnosed with hepatobiliary carcinoma. We expect high levels of chronic stress to be associated with (a) attempts to change maladaptive health behaviors or adopt adaptive health behaviors, or (b) attempts to decrease physiological arousal by continued use or re-initiation of maladaptive health behaviors. We expect that a positive illness perception will mediate the link between perceived stress and health behaviors and that problem focused coping and social support will moderate this relationship. Engaging in maladaptive behaviors to reduce stress will be mediated by negative illness perceptions and moderated by emotion focused coping and lack of social support; (3) to explore the links between stress, health behaviors, and biomarkers of inflammation on disease progression. We expect that patients with a combination of chronic stress and/or engagement in maladaptive health behaviors will have abnormal levels of biomarkers of inflammation and more rapid tumor growth and development of intra- and extra-hepatic metastases when compared to patients with lower levels of perceived stress or adaptive health behaviors. The proposed study is responsive to the RFA which request studies that will examine mediating and moderating factors such as individual demographic (age, gender/sex, ethnicity) and psychological (vulnerabilities, resilience) differences, risk factors, early exposure to stress. The findings of this study are expected to lead to potential psychological and behavioral targets for interventions to improve quality of life and reduce mortality in people diagnosed with cancer. PUBLIC HEALTH RELEVANCE: Stress may be defined as when the demands being placed on an individual are perceived as threatening or harmful and exceed the resources available to manage the stressor. The life threatening and unpredictable course of cancer makes it a particularly stressful life experience; however there is great variability in reported levels of stess by those diagnosed with cancer. Perceived stress has been found to be associated with increased risk of mortality across several populations including those diagnosed with cancer. As a result, it is critical to understand the underlying mechanisms involved in the link between stress and increased risk of mortality. The goal of the proposed study will be to examine the biobehavioral pathways linking stress with cancer progression. Early life experiences (e.g., adverse events) as well as behavioral pathways (e.g., tobacco use), and their contribution on inflammation in the periphery and tumor microenvironment, will be examined in regard to disease progression. The findings of the study are expected to facilitate the development and targeting of effective interventions for those diagnosed with cancer.